29.23 Nefazodone and Trazodone
997
and typical dosages. Phenelzine use should begin with a test
dose of 15 mg on the first day. The dosage can be increased to
15 mg three times daily during the first week and increased by
15 mg a day each week thereafter until the dosage of 90 mg a
day, in divided doses, is reached by the end of the fourth week.
Tranylcypromine and isocarboxazid use should begin with a test
dosage of 10 mg and may be increased to 10 mg three times
daily by the end of the first week. Many clinicians and research-
ers have recommended upper limits of 50 mg a day for isocar-
boxazid and 40 mg a day for tranylcypromine. Administration
of tranylcypromine in multiple small daily doses may reduce its
hypotensive effects.
Even though coadministration of MAOIs with TCAs, SSRIs,
or lithium is generally contraindicated, these combinations have
been used successfully and safely to treat patients with refractory
depression. However, they should be used with extreme caution.
Hepatic transaminase serum concentrations should be moni-
tored periodically because of the potential for hepatotoxicity,
especially with phenelzine and isocarboxazid. Elderly persons
may be more sensitive to MAOI adverse effects than are younger
adults. MAO activity increases with age, so MAOI dosages
for elderly persons are the same as those required for younger
adults. The use of MAOIs for children has had minimal study.
Studies have suggested that transdermal selegiline has anti-
depressant properties. Although selegiline is a type B inhibitor
at low doses, it becomes less selective as the dose is increased.
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▲▲
29.23 Nefazodone and
Trazodone
Nefazodone (Serzone) and Trazodone (Desyrel, Oleptro) are
mechanistically and structurally related drugs approved as treat-
ments for depression. Nefazodone (Serzone) is an analog of tra-
zodone. When nefazodone was introduced in 1995, there were
expectations that it would become widely used because it did
not cause the sexual side effects and sleep disruption associated
with the selective SSRIs. Although it was devoid of these side
effects, it was nevertheless found to produce problematic seda-
tion, nausea, dizziness, and visual disturbances. Consequently,
nefazodone was never extensively adopted in clinical practice.
This fact, as well as reports of rare cases of sometimes fatal
hepatotoxicity, led the original manufacturer to discontinue pro-
duction of branded nefazodone in 2004. Generic nefazodone
remains available in the United States.
Trazodone received Food and Drug Administration (FDA)
approval in 1981 as a treatment for major depressive disorder
(MDD). Its novel triazolopyridine chemical structure distin-
guished it from the TCAs, and clinical trials suggested improved
safety and tolerability compared with TCAs. There were high
expectations that it would replace the older drugs as a mainstay
of treatment for depression. However, the extreme sedation asso-
ciated with trazodone, even at subtherapeutic doses, limited the
clinical effectiveness of the drug. However, its soporific proper-
ties made trazodone a favorite alternative to standard hypnotics
as a sleep-inducing agent. Unlike conventional sleeping pills,
trazodone is not a controlled substance.
In 2010, the FDA approved an extended-release, once-daily
formulation (Oleptro) as a treatment for MDD in adults. In the
Table 29.22-3
Typical Dosage Forms and Recommended Dosages
for Currently Available Monoamine Oxidase
Inhibitors
Drug
Usual Dose
(mg/day)
Maximum
Dose
(mg/day)
Dosage (Oral)
Formulation
Isocarboxazid
(Marplan)
20–40
60
10-mg tablets
Phenelzine
(Nardil)
30–60
90
15-mg tablets
Tranylcypromine
(Parnate)
20–60
60
10-mg tablets
Rasagiline
0.5–1.0
1.0
0.5- or 1.0-mg
tablets
Selegiline
(Eldepryl)
10
30
5-mg tablets
Moclobemide
(Manerix)
300–600 600
100- or 150-mg
tablets
